A Cofactor-Based Mechanism for the Origin of the Genetic Code

Abstract

The origin of the genetic code is probably the central problem of the studies on the origin of life. The key question to answer is the molecular mechanism that allows the association of the amino acids with their triplet codons. We proposed that the codon-anticodon duplex located in the acceptor stem of primitive tRNAs would facilitate the chemical reactions required to synthesize cognate amino acids from simple amino acids (glycine, valine, and aspartic acid) linked to the 3′ acceptor end. In our view, various nucleotide-A-derived cofactors (with reactive chemical groups) may be attached to the codon-anticodon duplex, which allows group-transferring reactions from cofactors to simple amino acids, thereby producing the final amino acid. The nucleotide-A-derived cofactors could be incorporated into the RNA duplex (helix) by docking Adenosine (cofactor) into the minor groove via an interaction similar to the A-minor motif, forming a base triple between Adenosine and one complementary base pair of the duplex. Furthermore, we propose that this codon-anticodon duplex could initially catalyze a self-aminoacylation reaction with a simple amino acid. Therefore, the sequence of bases in the codon-anticodon duplex would determine the reactions that occurred during the formation of new amino acids for selective binding of nucleotide-A-derived cofactors.

The ‘LUCAN’ Concept, the Latest Universally Common Ancestral Network Stage of Early Life: From Molecular Cooperation and Horizontal Symbiosis to the Escape of Vertically Stabilized Lineages of Particulate Viral Propagules and Cellular Organisms

“…The controversial question of "Genetics First" or "Metabolism First" [45], which too long has been overshadowed by the tentative RNA World model of primordial RNA molecules having both replicative and catalytic functions on their own [121], can now be resolved by a more inclusive, network-expanding alternative as follows: The co-emergence of and further coevolution in functional partnerships between different types of macromolecular agents is receiving more attention, not the least in terms of the closely knit peptide/RNA partnership of a Peptide/RNA World scenario [83], which conceivably began by structurally complementary affinity already at the oligomeric level [122]. Circumstantial evidence suggests that the acceptor stem region of tRNA-like oligomers played a critical role for peptide growth as such and initial codon-anticodon interactions for the emergence of the genetic coding/decoding system as well [123][124][125][126][127].…”

Biological Catalysis and Information Storage Have Relied on N-Glycosyl Derivatives of β-D-Ribofuranose since the Origins of Life

“…Recently, this concept has been significantly modified, and new theories present the origin of life as RNA catalysis facilitated by amino acidor peptide-based cofactors or the "RNA-peptide World". Nevertheless, each scenario had to be based on the prebiotic synthesis of activated nucleotides and RNA molecules, including ribozymes [45][46][47][48][49][50][51][52][53][54][55]. Following this remark, the very origin of any RNA-based World(s) from inanimate matter appears particularly interesting.…”

“…It had two very important consequences: (i) the development of a genetic code, as a result of which, information encoding in the RNA and its transcription into proteins became possible, and (ii) the shift to protein-mediated catalysis [87]. The origin of genetic code could evolve through molecular recognition between pairs: primitive tRNA-specific amino acids, giving the chemical basis for a selective formation of aminoacyl-tRNA sets [54]. Although a simple peptide bond formation between two amino acids can be catalyzed by the RNA only [88], the formation of the ribosome, a large peptide-RNA assembly that forms the peptide bond between two specific amino acids based on the information encoded in RNA, appeared to be an evolutionary milestone [89].…”